Stress and its influence on Alzheimer’s disease

Aging is an inevitable journey for everyone, and includes many obstacles and different paths to take. How we live our lives can have enormous impact on whether we grow old gracefully, or succumb along the way. Good physical health, through diet and exercise, will allow people to remain active well into their twilight years, but as lifespan increases it is also important to take care of and maintain brain health as well. Fortunately, it appears that what is good for the heart is also good for the brain, and thus by keeping active, both physically and mentally, and maintaining a healthy diet rich in omega 3 fatty acids, a person can have the best chance of aging successfully, and avoid both heart disease and brain disease.

The major brain disease of the elderly is Alzheimer’s disease. It affects 1 in 20 people aged 65 and over, and its incidence increases with age such that around half of people aged 85 and over have the disease. Alzheimer’s disease is a devastating disorder that robs a person of their memories and cognitive abilities, rendering them unable to recognize family members, or care for themselves. But what is it that causes Alzheimer’s disease? Why do some people develop Alzheimer’s disease and not others? By asking, and then understanding these questions, we, as scientists, can develop therapies and strategies to help people avoid developing the disease in old age.

Here within UCI MIND, we have devoted considerable resources to identifying the causes of Alzheimer’s disease, and finding ways to circumvent these causes. We have identified how the stress hormone cortisol can play a role in the development of Alzheimer’s disease. Cortisol is a steroid hormone that is produced in the adrenal gland in response to times of stress. In the short term, following a stressful experience, cortisol levels rapidly increase in the blood stream, and its presence is helpful – improving short-term memory formation and adapting the body’s physiology to deal with the situation effectively. However, long-term stress leads to prolonged elevated levels of cortisol within the blood stream, which can have serious deleterious effects.

It was found, over twenty years ago, that patients with Alzheimer’s disease had elevated levels of cortisol in their blood streams, compared to healthy patients. This elevation correlated with the degree of memory impairments that the patients had and appeared early on in the disease progression. We were interested in whether or not these early increases in circulating cortisol could be contributing to the development of Alzheimer’s disease, by leading to the pathologies that are found in the AD brain. It is the accumulation of sticky proteins in the brain, leading to a loss of neuronal function, which underlies the dementia and memory loss seen in Alzheimer’s disease. Typically 2 sticky proteins are present in the Alzheimer’s disease brain – the first is the amyloid-beta peptide (Ab), which stick together inbetween neurons and form the extracellular plaques. The second sticky protein is known as tau, which becomes modified in the Alzheimer’s disease brain causing it to stick together inside neurons and disrupting normal neuronal function. The net result of these sticky proteins is a cascade of events leading to widespread synaptic and neuronal loss in the brain, which causes the dementia and memory loss.

Relax! Avoid stress...

We showed that cells treated with cortisol produced dramatically larger amounts of this Ab peptide – which can accumulate to form the Ab plaques. In order to test whether increased cortisol could have a similar effect in animals and by extension people we turned to a genetically altered mouse, which had been engineered to develop Alzheimer’s disease pathology in its brain as it aged. We took young animals, before they were old enough to have Alzheimer’s disease pathology, and we injected them with a rodent equivalent of cortisol every day for 1 week. After just a single week we looked inside the brains of these animals and found that levels of both Ab peptide and tau protein were tremendously elevated. This showed us that increases in circulating cortisol in humans is able to increase the pathology present in the brain – and thus could make people develop Alzheimer’s disease faster.

So how can we use these findings to help people reduce their risk of developing Alzheimer’s disease in old age? Firstly, cortisol levels are increased by stress – a study has also shown that people with stressful lives are around 2-3 times more likely to develop Alzheimer’s disease than others. So avoiding stress is paramount. In addition, these results can be used by scientists to develop drugs to block either the production of cortisol, or to prevent its effects once it is produced. This could lead to a slowing of the disease if it proves successful.

Stress reduction, combined with a healthy lifestyle and diet will help people age successfully and avoid disease.